This application is for research training and development of an immunobiologist interested in the role of the brain and behavior in modulation and regulation of immune function and host resistance to disease. The proposed research is directed toward understanding the role of stressful environmental stimuli and the host's control over its environment, on the immune system and defense against viral disease. To achieve this, a murine model of herpesvirus type 1 (HSV1) infections will be studied, in which resistance mechanisms have been reasonably well characterized. The impact of acute or chronic, predictable or unpredictable stress (mild electric footshock) will be analyzed. Furthermore, the important variable of control, in the form of escapable, vs. yoked-inescapable shock, will be assessed, as will the loss of control once it has been learned. The role of the sympathetic nervous system in mediating the immunological consequence of stress will be evaluated by modifying peripheral catecholamines and beta adrenergic receptors with pharmacological agents. The effects of the above behavioral and neural manipulations on a number of immune functions and on natural resistance and acquired immunity to HSV1 infection will be examined. Specifically, interferon production and natural killer cell activity will be evaluated as major mediators of natural resistance. The generation of virus-specific cytotoxic T lymphocytes, antiviral delayed hypersensitivity responses, and the production of HSV-specific antibodies will be studied as the agents of acquired immunity. Finally, studies will be initiated to examine the role of stress and the sympathetic nervous system in latent infections and virus reaction. This combined approach should result in a greater understanding of the role of psychosocial variables, and their neural mechanisms, in immunology and infectious disease. Such interdisciplinary research necessitates additional training of the applicant in the behavioral and neurosciences, and will be achieved thrugh collaborative research at the home institution, some formal training, and time spent in other laboratories.